title: Chromium(III) oxide nanoparticles induced remarkable oxidative stress and apoptosis on culture cells.
abstract: Chromium(III) oxide (Cr(2)O(3)) is used for industrial applications such as catalysts and pigments. In the classical form, namely the fine particle, Cr(2)O(3) is insoluble and chemically stable. It is classified as a low-toxicity chromium compound. Recently, industrial application of nanoparticles (a new form composed of small particles with a diameter of ≤100 nm, in at least one dimension) has been increasing. Cellular effects induced by Cr(2)O(3) nanoparticles are not known. To shed light upon this, the release of soluble chromium from Cr(2)O(3) nano- and fine-particles in culture medium was compared. Fine Cr(2)O(3) particles were insoluble in the culture medium; on the contrary, Cr(2)O(3) nanoparticles released soluble hexavalent chromium into the culture medium. Cr(2)O(3) nanoparticles showed severe cytotoxicity. The effect of Cr(2)O(3) nanoparticles on cell viability was higher than that of fine particles. Cr(2)O(3) nanoparticles showed cytotoxicity equal to that of hexavalent chromium (K(2)Cr(2)O(7)). Human lung carcinoma A549 cells and human keratinocyte HaCaT cells showed an increase in intracellular reactive oxygen species (ROS) level and activation of antioxidant defense systems on exposure to Cr(2)O(3) nanoparticles. Exposure of Cr(2)O(3) nanoparticles led to caspase-3 activation, showing that the decrease in cell viability by exposure to Cr(2)O(3) nanoparticles was caused by apoptosis. Cellular responses were stronger in the Cr(2)O(3) nanoparticles-exposed cells than in fine Cr(2)O(3) - and CrCl(3) -exposed cells. Cellular uptake of Cr(2)O(3) particles were observed in nano- and fine-particles. The cellular influence of the extracellular soluble trivalent chromium was lower than that of Cr(2)O(3) nanoparticles. Cr(2)O(3) nanoparticles showed cytotoxicity by hexavalent chromium released at outside and inside of cells. The cellular influences of Cr(2)O(3) nanoparticles matched those of hexavalent chromium. In conclusion, Cr(2)O(3) nanoparticles have a high cytotoxic potential.
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology, 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577, Japan. masa-horie@aist.go.jp
authors.forename: Masanori
authors.initials: M
authors.lastname: Horie
authors.forename: Keiko
authors.initials: K
authors.lastname: Nishio
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Endoh
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Kato
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Fujita
authors.forename: Arisa
authors.initials: A
authors.lastname: Miyauchi
authors.forename: Ayako
authors.initials: A
authors.lastname: Nakamura
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kinugasa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Etsuo
authors.initials: E
authors.lastname: Niki
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Iwahashi
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002857:Chromium / Q000737:chemistry; D017608:Chromium Compounds / Q000494:pharmacology*; D003470:Culture Media / Q000737:chemistry; D004249:DNA Damage; D005978:Glutathione / Q000032:analysis; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D053758:Nanoparticles; D018384:Oxidative Stress / Q000187:drug effects*; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017608:Chromium Compounds; D003470:Culture Media; D017382:Reactive Oxygen Species; D002857:Chromium; C074702:chromium hexavalent ion; C505407:CASP3 protein, human; D053148:Caspase 3; D005978:Glutathione; C023600:chromic oxide